The expression pattern of the mouse receptor tyrosine kinase gene MDK1 is conserved through evolution and requires Hoxa-2 for rhombomere-specific expression in mouse embryos
The expression pattern of the mouse receptor tyrosine kinase gene MDK1 is conserved through evolution and requires Hoxa-2 for rhombomere-specific expression in mouse embryos
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DOI：
10.1006/dbio.1996.0173
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发表时间：
1996-08-01
影响因子：
2.7
通讯作者：
Chambon, P
中科院分区：
文献类型：
--
作者：
Taneja, R;Thisse, B;Chambon, P
后脑的分割在整个脊椎动物物种中都是保守的，并导致了菱形脑的瞬时形成，这是血统限制的间隔。对分割过程的分子机制的研究表明，菱形边界与几个进化保守基因的表达界限一致，如锌指转录因子KROX-20和同源框基因，它们以特定的时空顺序表达，已被证明是片段同一性的重要调节因子。除了KROX-20和HOX基因外，受体蛋白酪氨酸激酶(RTK)Eph亚家族的几个成员也在后脑以片段受限的方式表达，这表明这些受体可能与HOX基因协同作用，以建立区域认同。在导致片段同一性的一系列调控相互作用中，KROX-20似乎作用于HOX基因的上游，但下游效应者的身份尚未确定。我们报道了小鼠RTK基因MDK1的斑马鱼同源基因的分离，该基因属于Eph受体亚家族，并表明小鼠和斑马鱼基因的主要表达结构域在进化过程中是保守的。由于HOXA-2和MDK1在小鼠后脑中表达的时空一致性提示它们之间可能存在调控联系，我们分析了HOXA-2缺失突变胚胎中MDK1的表达。在HOXA-2突变体后脑的菱形核3中，MDK1的表达选择性缺失，而在其他菱形核中的表达模式发生了全面的变化，从而证明MDK1在形态发生信号级联中位于HOXA-2的下游。(C)1996年学术出版社。
Segmentation of the hindbrain has been conserved throughout the vertebrate species and results in the transient formation of rhombomeres, which are lineage-restricted compartments. Studies on the molecular mechanisms underlying the segmentation process have revealed that rhombomeric boundaries coincide with the expression limits of several evolutionary conserved genes such as the zinc-finger transcription factor Krox-20 and homeobox genes which are expressed in a specific spatial and temporal order and have been shown to be important regulators of segmental identity. In addition to Krox-20 and Hox genes, several members of the Eph subfamily of receptor protein tyrosine kinase (RTK) genes are also expressed in a segment-restricted manner in the hindbrain, suggesting that these receptors may act in concert with Hox genes to establish regional identity. In the cascade of regulatory interactions leading to segmental identity, Krox-20 appears to act ''upstream'' of Hox genes, but the identity of the ''downstream'' effecters has not yet been identified. We report here the isolation of the zebrafish orthologue of the mouse RTK gene MDK1 which belongs to the Eph receptor subfamily and show that the major expression domains of the mouse and the zebrafish genes have been conserved through evolution. Since the coincident spatial and temporal expression of Hoxa-2 and MDK1 in the mouse hindbrain suggested a possible regulatory link between them, we analyzed the expression of the MDK1 in Hoxa-2 null mutant embryos. A selective lack of MDK1 expression in rhombomere 3 of Hoxa-2 mutant hindbrains together with an overall altered expression pattern in the other rhombomeres was observed, thus demonstrating that MDK1 lies downstream of Hoxa-2 in the morphogenetic signaling cascade. (C) 1996 Academic Press, Inc.